Hemostasis and Thrombosis Issues

APRIL 17, 2011

Charles H. Brown, MSPharm, RPh, CACP

Green, Not Black, Tea May Reduce Risk of CAD

Green tea catechins have been studied and shown to inhibit oxidation, vascular inflammation, atherogenesis, and thrombogenesis and to favorably modulate the plasma lipid profile and vascular reactivity, which suggests a wide spectrum of beneficial effects on coronary artery disease (CAD). Because of the different degrees of fermentation, the content and composition of catechins vary substantially in black and green tea. For patients taking warfarin, drinking excessive amounts of green tea may be problematic, because green tea contains vitamin K (an antagonist of warfarin) and international normalized ratio measurements may become erratic. Unfortunately, the contents of green tea drinks may not list vitamin K as an ingredient, so patients need to be aware of this fact.

Antiplatelet Therapy 101

When platelets react to extravascular tissue or chemicals, they undergo a variety of changes known as platelet activation to become active participants in the hemostasis process. The final outcome of platelet activation includes enhancement of platelet procoagulant activity through multiple interactions between chemicals, endothelium, and platelets to form multiple platelet aggregation events and the generation of a platelet-rich thrombus to terminate bleeding. The rationale for using antiplatelet drugs or platelet aggregation inhibitor (PAI) therapy is to partially or completely prevent the participation of platelets in the thrombus formation, extension, and embolization.

Currently, there are 3 primary types of PAIs available in the United States: 1) cyclooxygenase inhibitors or metabolic inhibitors of thromboxane A 2 [TX A 2 ] include aspirin and nonsteroidal anti-inflammatory drugs; of these, only aspirin irreversibly binds to platelets; 2) thienophyridines (irreversibly binds to the platelet P2Y 12 receptors) include ticlopidine, clopidogrel, and prasugrel. Platelet receptor P2Y 12 activation is required to amplify and sustain ADP-induced platelet aggregation. Thienophyridines are oral prodrugs and yield additive inhibition of platelet function when administered with aspirin because 2 different pathways of irreversible platelet activation are inhibited for the 7- to 10-day life of platelets; and 3) glycoprotein (GP) Ilb-IIIa receptor inhibitors and includes abciximab, tirofiban, and eptifibatide. These intravenous drugs inhibit the final common pathway of platelet aggregation where fibrinogen binds to GP IIb/IIIa receptor.

An Aspirin a Day May Not Keep the Doctor Away

A spirin, a widely used antiplatelet agent worldwide, just celebrated its 111th year. Its efficacy has made it the cornerstone of therapy in patients with coronary artery disease (CAD). Daily doses of aspirin 40 mg reduce the risk of stroke, myocardial infarction, and death by about 25%. There is no clear evidence that doses higher than 100 mg per day increase its antithrombotic efficacy. For this reason, a fixed regimen of once daily low-dose aspirin has been adopted into all relevant treatment guidelines.

Although it is true in most cases that an aspirin a day keeps the doctor away, it would also appear that not all patients benefit from the drug to the same degree. A recent study by Henry et al explored whether once daily low-dose aspirin provides sustained inhibition of platelet function throughout the 24-hour dosing interval of stable CAD patients. The major finding was that in up to 25% of patients, platelets recover their ability to aggregate within 24 hours of the last aspirin dose, thus potentially leaving patients unprotected against thrombotic events at the end of the dosing interval. Reasons to explain this lack of response are unclear.

A New Score for Stroke Prediction in AF: CHA2DS2-VASc

A new, more sensitive score for assessing the likelihood of stroke in patients with atrial fibrillation (AF), called CHA 2 DS 2 - VASc, enables further refinement of risk compared with traditional CHADS 2 at predicting those who will have a stroke over 10 years. The new score appears to be better at identifying people at very low risk, “those who likely do not need anticoagulation,” and thus may be a better alternative to the older criteria. A study by Olesen et al reported that 8.7% of subjects were considered low risk using the new score, compared with 22.3% using the old criteria. Using the new criteria, for a patient with a score of ≥2, representing 1 major risk factor or 2 or more clinically relevant nonmajor risk factors, oral anticoagulation is recommended. For a score of 1 or 0, the recommendation would range from receiving oral anticoagulation or oral aspirin dosed at 75 to 325 mg daily to no antithrombotic therapy.

Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, West Lafayette, Indiana. This column’s information is based on current studies and references, but it may be changed without notice with newer studies or with different patient populations.